The heavy metals mercury, metyl mercury, and cadmium perturb AIB transport across human placental syncytiotrophoblast tissue. Inorganic mercury produces a transient increase in early AIB transport, but all three of these heavy metal compounds ultimately inhibit AIB transport and disrupt normal transport kinetics. Cysteine will protect against the effects of mercuric chloride and methyl mercuric chloride but will not reverse their effects, indicating strong metal-membrane interaction. Mercuric chloride may physically disrupt the integrity of the placental vesicles causing an initial increase in membrane permeability and ultimately a disruption of permeability. The preincubation time requirement may be necessary to allow the mercuric ion to penetrate the membrane and subsequently alter its integrity. Methyl mercury and cadmium may act more specifically in inhibiting AIB transport and not effect general membrane integrity since, unlike inorganic mercury, neither methylmercury nor cadmium alter vesicular AIB equilibrium. Methyl mercuric chloride and cadmium chloride may penetrate the placental vesicular membrane more readily since a long preincubation is not required for these metals to alter AIB transport. The techniques used in this investigation represent a novel method to investigate the effects of toxic compounds on human tissue. The effects of mercuric chloride, methyl mercuric chloride, and cadmium chloride on the human placental tissue preparation described may explain the fetotoxic effects of these metals. The inhibition of AIB transport by methyl mercuric chloride and cadmium chloride may be more deleterious than the stimulatory effect on AIB transport of mercuric chloride. Methyl mercury and cadmium (II) have strong demonstrable fetotoxic effects while mercury (II) appears much less fetotoxic. The preincubation time requirement for observation of mercuric chloride effects on AIB may reflect ability to cross the placental membranes.